关键词: METTL14 Mitochondrial damage Osteoporosis SLC25A3

Mesh : Osteoblasts / metabolism Animals Mice Female Humans Osteoporosis / metabolism Mitochondria / metabolism Ovariectomy Osteogenesis Cell Differentiation Methyltransferases / metabolism genetics Membrane Potential, Mitochondrial Signal Transduction Methylation Reactive Oxygen Species / metabolism Disease Models, Animal Mice, Inbred C57BL

来  源:   DOI:10.1016/j.exger.2024.112496

Abstract:
OBJECTIVE: Osteoporosis is linked to impaired function of osteoblasts, and decreased expression of METTL14 may result in abnormal differentiation of these bone-forming cells. However, the specific impact of METTL14 on osteoblast differentiation and its underlying mechanisms are not yet fully understood.
RESULTS: This study discovered a positive correlation between METTL14 expression and bone formation in specimens from osteoporosis patients and ovariectomized (OVX) mice. Additionally, METTL14 targeting of SLC25A3 contributed to the restoration of mitochondrial ROS levels and mitochondrial membrane potential in osteoblasts and promoted osteoblast differentiation. Moreover, in vivo experiments showed that METTL14 enhanced bone formation, and therapeutic introduction of METTL14 countered the decrease in bone formation in OVX mice.
CONCLUSIONS: Overall, these findings emphasize the crucial role of the METTL14/SLC25A3 signaling axis in osteoblast activity, suggesting that this axis could be a potential target for improving osteoporosis.
摘要:
目的:骨质疏松与成骨细胞功能受损有关,METTL14的表达降低可能导致这些骨形成细胞的异常分化。然而,METTL14对成骨细胞分化的具体影响及其潜在机制尚不完全清楚.
结果:这项研究发现,骨质疏松症患者和卵巢切除(OVX)小鼠的标本中,METTL14表达与骨形成之间呈正相关。此外,METTL14靶向SLC25A3有助于成骨细胞线粒体ROS水平和线粒体膜电位的恢复,促进成骨细胞分化。此外,体内实验表明,METTL14增强了骨形成,METTL14的治疗性引入抵消了OVX小鼠骨形成的减少。
结论:总体而言,这些发现强调了METTL14/SLC25A3信号轴在成骨细胞活性中的关键作用,表明该轴可能是改善骨质疏松症的潜在目标。
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